Large proportions of overweight and obese children, as well as their parents, underestimate children's weight status across Europe. The ENERGY (EuropeaN Energy balance Research to prevent excessive weight Gain among Youth) project.
To investigate the magnitude and country-specific differences in underestimation of children's weight status by children and their parents in Europe and to further explore its associations with family characteristics and sociodemographic factors. Children's weight and height were objectively measured. Parental anthropometric and sociodemographic data were self-reported. Children and their parents were asked to comment on children's weight status based on five-point Likert-type scales, ranging from 'I am much too thin' to 'I am much too fat' (children) and 'My child's weight is way too little' to 'My child's weight is way too much' (parents). These data were combined with children's actual weight status, in order to assess underestimation of children's weight status by children themselves and by their parents, respectively. Chi-square tests and multilevel logistic regression analyses were conducted to examine the aims of the current study. Eight European countries participating in the ENERGY (EuropeaN Energy balance Research to prevent excessive weight Gain among Youth) project. A school-based survey among 6113 children aged 10-12 years and their parents. In the total sample, 42·9 % of overweight/obese children and 27·6 % of parents of overweight/obese children underestimated their and their children's weight status, respectively. A higher likelihood for this underestimation of weight status by children and their parents was observed in Eastern and Southern compared with Central/Northern countries. Overweight or obese parents (OR=1·81; 95 % CI 1·39, 2·35 and OR=1·78, 95 % CI 1·22, 2·60), parents of boys (OR=1·32; 95 % CI 1·05, 1·67) and children from overweight/obese (OR=1·60; 95 % CI 1·29, 1·98 and OR=1·76; 95 % CI 1·29, 2·41) or unemployed parents (OR=1·53; 95 % CI 1·22, 1·92) were more likely to underestimate children's weight status. Children of overweight or obese parents, those from Eastern and Southern Europe, boys, younger children and children with unemployed parents were more likely to underestimate their actual weight status. Overweight or obese parents and parents of boys were more likely to underestimate the actual weight status of their children. In obesity prevention such underestimation may be a barrier for behavioural change.


Micronutrient intakes of lactating mothers and their association with breast milk concentrations and micronutrient adequacy of exclusively breastfed Indonesian infants.
Breast milk is the sole source of nutrition for exclusively breastfed infants in the first 6 mo of life, yet few studies have measured micronutrient concentrations in breast milk in light of maternal diet and subsequent infant micronutrient intakes. We evaluated the adequacy of micronutrient intakes of exclusively breastfed Indonesian infants by measuring milk volume and micronutrient concentrations and assessed maternal micronutrient intakes and their relationship with milk concentrations. Mother-infant (2-5.3 mo) dyads (n = 113) were recruited for this cross-sectional study. Volume of breast-milk intake via the deuterium dose-to-mother technique over 14 d and analyzed micronutrient concentrations were used to calculate micronutrient intakes of exclusively breastfed infants. Maternal 3-d weighed food records were collected to assess median (IQR) micronutrient intakes. Multivariate regression analyses examined the association of usual maternal micronutrient intakes with milk micronutrient concentrations after adjustment for confounding variables. Mean ± SD intake of breast-milk volume was 787 ± 148 mL/d. Median daily infant intakes of iron, zinc, selenium, magnesium, sodium, and B-vitamins (thiamin, riboflavin, niacin, pantothenic acid, B-6, and B-12) were below their respective Adequate Intakes. Inadequacies in maternal intakes (as % < estimated average requirements) were >40% for calcium, niacin, and vitamins A, B-6, and B-12. Significant positive associations existed between maternal usual intakes of vitamin A, niacin and riboflavin and milk retinol, nicotinamide, and free riboflavin concentrations in both unadjusted and adjusted (for infant age, milk volume, and parity) analyses (all P < 0.05). The majority of micronutrient intakes for these exclusively breastfed infants and their mothers fell below recommendations, with associations between maternal intakes and breast-milk concentrations for 3 nutrients. Data on nutrient requirements of exclusively breastfed infants are limited, and a better understanding of the influence of maternal nutritional status on milk nutrient concentrations and its impact on the breastfed infant is needed.


Fast BK-type channel mediates the Ca(2+)-activated K(+) current in crayfish muscle.
The role of the Ca(2+)-activated K(+) current (I(K(Ca))) in crayfish opener muscle fibers is functionally important because it regulates the graded electrical activity that is characteristic of these fibers. Using the cell-attached and inside-out configurations of the patch-clamp technique, we found three different classes of channels with properties that matched those expected of the three different ionic channels mediating the depolarization-activated macroscopic currents previously described (Ca(2+), K(+), and Ca(2+)-dependent K(+) currents). We investigated the properties of the ionic channels mediating the extremely fast activating and persistent I(K(Ca)). These voltage- and Ca(2+)-activated channels had a mean single-channel conductance of approximately 70 pS and showed a very fast activation. Both the single-channel open probability and the speed of activation increased with depolarization. Both parameters also increased in inside-out patches, i.e., in high Ca(2+) concentration. Intracellular loading with the Ca(2+) chelator bis(2-aminophenoxy) ethane-N, N,N',N'-tetraacetic acid gradually reduced and eventually prevented channel openings. The channels opened at very brief delays after the pulse depolarization onset (<5 ms), and the time-dependent open probability was constant during sustained depolarization (< or =560 ms), matching both the extremely fast activation kinetics and the persistent nature of the macroscopic I(K(Ca)). However, the intrinsic properties of these single channels do not account for the partial apparent inactivation of the macroscopic I(K(Ca)), which probably reflects temporal Ca(2+) variations in the whole muscle fiber. We conclude that the channels mediating I(K(Ca)) in crayfish muscle are voltage- and Ca(2+)-gated BK channels with relatively small conductance. The intrinsic properties of these channels allow them to act as precise Ca(2+) sensors that supply the exact feedback current needed to control the graded electrical activity and therefore the contraction of opener muscle fibers.


Digit force adjustments during finger addition/removal in multi-digit prehension.
We explored adjustments in multi-digit coordinated action on a hand-held object with finger addition and removal. The subjects (n = 7) kept a vertically oriented handle at rest using a prismatic grasp as if holding a glass of liquid and then either added one finger to the grasp, the index (I) or little (L) finger, or removed one finger. Three external torques were applied on the apparatus: clockwise, counterclockwise, and no torque. The individual digit forces and moments were recorded with six-component sensors. The change in grasping force, normal force of the thumb and virtual finger (VF, an imagined finger that generates the same mechanical effect as all fingers together), depended on the function of the manipulated finger, i.e. on whether the finger resisted external torque (torque agonist) or assisted it (torque antagonist). There was a significant increase of the grasping force when an antagonist was added or when an agonist was removed. These force increases were not necessary for slipping prevention: the normal forces prior to the manipulation were large enough to prevent slipping. All other finger manipulations exhibited no significant change in the grip force, except for the antagonist removal during the supination efforts (after removing the I finger the grasping force decreased). In contrast, the changes in the tangential force of the thumb depended on the manipulated finger, not on the finger function with respect to external torque. There was a significant thumb tangential force increase when the I finger was added or when the L finger was removed; opposite changes were seen when the L finger was added or the I finger was removed. The changes of the virtual finger (VF) tangential force were equal and opposite to the thumb tangential force alterations; these opposite changes caused changes in the moments, these forces generated. The changes in the moments of the tangential forces were counterbalanced by the opposite changes in the moments of normal forces such that the total moment remained constant and the handle orientation was maintained. At the level of individual finger (IF) forces two strategies of error compensation were found: (a) local error compensation--the opposite action of the neighboring finger, i.e. force decrease in response to a force increase (finger addition), and vice versa and (b) distant error compensation--similar action by a finger that is a torque antagonist to the manipulated finger. During the transient periods, the changes in the thumb and VF forces were simultaneous and equal in magnitude. The normal forces increased or decreased concurrently while the changes in the tangential forces were opposite in direction. The data support the existence of chain effects in the digit force adjustments to finger addition or removal. We conclude that the digit force adjustments during the object manipulation are controlled mainly in a feed-forward manner. The obtained data agree with the principle of superposition reported previously. The findings agree with earlier reports on the limited ability of CNS to organize synergies at two levels of a control hierarchy simultaneously.


Indirect measurements of sweat electrolyte concentration in the laboratory diagnosis of cystic fibrosis.
To investigate whether analytical methods based on the colligative physical chemical properties of ions or solutes in sweat are less effective than the specific measurement of electrolytes in the diagnosis of cystic fibrosis (CF). A single sweat sample was collected (Macroduct) from each of 211 infants and children, of whom 57 had CF, for the measurement of sodium, chloride, osmolality, and conductivity. The ranges within which CF and non-CF individual values overlapped (equivocal ranges), were wider for sodium and osmolality measurement than for chloride or conductivity. Neither of the latter two measurements provided a discriminatory advantage over the other. The utilisation of broadly based age related ranges for non-CF control subjects served to improve the discriminatory power of all four measurements to an extent that, in this cohort, both chloride and conductivity provided complete discrimination. Sweat conductivity is as effective as chloride measurement in the laboratory diagnosis of CF.


Gender differences in time-frequency EMG analysis of unanticipated cutting maneuvers.
The purpose of this study is to compare the time-frequency characteristic, using nonlinearly scaled wavelets, of the EMG signal as well as the three-dimensional (3D) knee kinematics of female and male elite soccer players performing an unanticipated cutting maneuver. Fifteen female and 15 male elite soccer players performed several cutting maneuvers during which EMG of eight muscles of the leg and 3D kinematics of the knee were recorded. To create an unanticipated condition, the participants executed one of three tasks, which were signaled to them with an illuminated target board. Male participants generally executed the unanticipated cutting maneuver with a quadriceps activation of higher frequency components. These gender differences were also found at initial ground contact (IC) for the vastii and biceps femoris (BF) muscles. These higher frequencies dominated the signal earlier in time for the BF and later for the tibialis anterior (TA) in women. Furthermore, women performed the cutting task with greater knee abduction than did the men. Female athletes adopted a different motor unit recruitment strategy that was particularly evident at, and near, IC resulting in lower frequency components in the EMG signal of the lateral hamstring. This strategy may play a role in explaining the gender bias in anterior cruciate ligament (ACL) injury rates. Gender differences in knee kinematics were also observed, exposing the female ACL to higher strain, which may be the result of differences in neuromuscular strategies to stabilize the knee joint.


NUSAP1 promotes invasion and metastasis of prostate cancer.
We have previously identified nucleolar and spindle associated protein 1 (NUSAP1) as a prognostic biomarker in early stage prostate cancer. To better understand the role of NUSAP1 in prostate cancer progression, we tested the effects of increased and decreased NUSAP1 expression in cell lines, in vivo models, and patient samples. NUSAP1 promotes invasion, migration, and metastasis, possibly by modulating family with sequence similarity 101 member B (FAM101B), a transforming growth factor beta 1 (TGFβ1) signaling effector involved in the epithelial to mesenchymal transition. Our findings provide insights into the importance of NUSAP1 in prostate cancer progression and provide a rationale for further study of NUSAP1 function, regulation, and clinical utility.


Functional dedifferentiation of associative resting state networks in older adults - A longitudinal study.
Healthy aging is associated with weaker functional connectivity within resting state brain networks and stronger functional interaction between these networks. This phenomenon has been characterized as reduced functional segregation and has been investigated mainly in cross-sectional studies. Here, we used a longitudinal dataset which consisted of four occasions of resting state fMRI and psychometric cognitive ability data, collected from a sample of healthy older adults (baseline N = 232, age range: 64-87 y, age M = 70.8 y), to investigate the functional segregation of several well-defined resting state networks encompassing the whole brain. We characterized the ratio of within-network and between-network correlations via the well-established segregation index. Our findings showed a decrease over a 4-year interval in the functional segregation of the default mode, frontoparietal control and salience ventral attention networks. In contrast, we showed an increase in the segregation of the limbic network over the same interval. More importantly, the rate of change in functional segregation of the frontoparietal control network was associated with the rate of change in processing speed. These findings support the hypothesis of functional dedifferentiation in healthy aging as well as its role in cognitive function in elderly.


Expression of p53 protein is an early event in ultraviolet light-induced cutaneous squamous cell carcinogenesis.
p53 Is known to be a tumor-suppressor gene and has been suggested to play an important role for multistep carcinogenesis of cutaneous squamous cell carcinoma (SCC). To evaluate the role of ultraviolet light (UV) in p53 mutation in squamous cell carcinogenesis, paraffin-embedded sections of SCCs were immunohistochemically stained with the CM-1 antibody for p53 protein. Positive staining suggests mutation of the p53 gene since the mutant p53 protein gains prolonged half-life to be detectable by this method. The specimen included SCCs induced by UV (SCCs on sun-exposed areas, SCCs on patients with xeroderma pigmentosum), roentgen rays, scar, and miscellaneous causes. In addition, solar keratoses that are precancerous lesions of UV-related SCCs were also analyzed. Fourteen (54%) of 26 UV-related SCCs were positive, whereas five (19%) of 26 UV-unrelated SCCs were positive. Among the UV-related SCCs, five (45%) of 11 well-differentiated SCCs and nine (60%) of 15 moderately to poorly differentiated SCCs were positive. Eleven (48%) of 23 solar keratoses were positive for p53. These results indicate that UV acts as a mutagen for the p53 gene, and this event may occur at a relatively early stage of multistep UV carcinogenesis.


Comparative analysis of atypical spitz tumors with heterozygous versus homozygous 9p21 deletions for clinical outcomes, histomorphology, BRAF mutation, and p16 expression.
Studies have shown that atypical Spitz tumors (ASTs) with homozygous deletions in 9p21 have worse prognosis than those without this finding. Conversely, numerous studies have shown that a range of other copy number aberrations including isolated 6q23 or 3p21 loss may be seen in ASTs without conferring higher risk for aggressive behavior. We studied 31 cases of ASTs with heterozygous 9p21 loss and hypothesize that heterozygous 9p21 loss in ASTs does not confer an increased risk for aggressive behavior. We compared clinical, histopathologic, and immunohistochemical features of 31 ASTs with heterozygous 9p21 deletions with 30 ASTs with homozygous 9p21 deletions. No ASTs with heterozygous 9p21 deletions resulted in distant metastasis. Severe cytologic atypia, a predominance of epithelioid cytomorphology and increased dermal mitotic activity were more frequent in ASTs with homozygous deletions versus ASTs with heterozygous deletions (P=0.0003, 0.0004, and 0.042, respectively). Expression of p16 and mutated BRAF proteins was also evaluated in 17 conventional (nonspitzoid) melanomas with homozygous 9p21 loss and the 2 groups of ASTs. Expression of p16 was retained in 67% of ASTs with heterozygous loss, whereas among ASTs with homozygous loss, 100% of cases had areas with complete loss of staining. Mutated BRAF protein expression was detected in 53% of conventional melanomas, in none of the ASTs with heterozygous loss, and in 1 AST with homozygous loss (P=0.0007 between homozygous ASTs and the conventional melanomas). Coexisting BRAF mutation and 9p21 deletion was more common in conventional melanomas than in ASTs with heterozygous or homozygous 9p21 deletion. BRAF mutation was highly uncommon among the ASTs.


High diagnostic accuracy of automated rapid Strep A test reduces antibiotic prescriptions for children in the United Arab Emirates.
Diagnosis of Group A Streptococcus (GAS) pharyngitis in children is hindered by variable sensitivity of clinical criteria and rapid Strep A tests (SAT), resulting in reliance on throat cultures as the gold standard for diagnosis. Delays while awaiting culture reports result in unnecessary antibiotic prescriptions among children, contributing to the spread of antimicrobial resistance (AMR). Diagnostic accuracy study of an automated SAT (A-SAT) in children up to 16 years of age presenting to an emergency room with signs and symptoms of pharyngitis between March and June 2019. Paired throat swabs for A-SAT and culture were collected. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for A-SAT were calculated. Two hundred and ninety-one children were included in this study. 168 (57.7%) were boys and the mean age was 4.2 years. A-SAT was positive in 94 (32.3%) and throat culture was positive in 90 (30.9%) children. A-SAT and throat culture results showed a high level of consistency in our cohort. Only 6 (2%) children had inconsistent results, demonstrating that the A-SAT has a high sensitivity (98.9%), specificity (97.5%), PPV (94.7%) and NPV (99.5%) for the diagnosis of GAS pharyngitis in children. Only 92 (32%) children were prescribed antibiotics while the vast majority (68%) were not. A-SAT is a quick and reliable test with diagnostic accuracy comparable to throat culture. Its widespread clinical use can help limit antibiotic prescriptions to children presenting with pharyngitis, thus limiting the spread of AMR.


Acquired degenerative changes of the intervertebral segments at and suprajacent to the lumbosacral junction. A radioanatomic analysis of the nondiskal structures of the spinal column and perispinal soft tissues.
In earlier evolutionary times, mammals were primarily quadrupeds. However, other bipeds have also been represented during the course of the Earth's several billion year history. In many cases, either the bipedal stance yielded a large tail and hypoplastic upper extremities (e.g., Tyrannosaurus rex and the kangaroo), or it culminated in hypoplasia of the tail and further development and specialization of the upper extremities (e.g., nonhuman primates and human beings). In the human species this relatively recently acquired posture resulted in a more or less pronounced lumbosacral kyphosis. In turn, certain compensatory anatomic features have since occurred. These include the normal characteristic posteriorly directed wedge-shape of the L5 vertebral body and the L5-S1 intervertebral disk; the L4 vertebral body and the L4-L5 disk may be similarly visibly affected. These compensatory mechanisms, however, have proved to be functionally inadequate over the long term of the human life span. Upright posture also leads to increased weight bearing in humans that progressively causes excess stresses at and suprajacent to the lumbosacral junction. These combined factors result in accelerated aging and degenerative changes and a predisposition to frank biomechanical failure of the subcomponents of the spinal column in these spinal segments. One other specific problem that occurs at the lumbosacral junction that predisposes toward premature degeneration is the singular relationship that exists between a normally mobile segment of spine (i.e., the lumbar spine) and a normally immobile one (i.e., the sacrum). It is well known that mobile spinal segments adjacent to congenitally or acquired fused segments have a predilection toward accelerated degenerative changes. The only segment of the spine in which this is invariably normally true is at the lumbosacral junction (i.e., the unfused lumbar spine adjoining the fused sacrum). Nevertheless, biomechanical failures of the human spine are not lethal traits; in most cases today, mankind reaches sexual maturity before spinal biomechanical failure precludes sexual reproduction. For this gene-preserving reason, degenerative spinal disorders will likely be a part of modern societies for the foreseeable eternity of the race. The detailed alterations accruing from the interrelated consequences of and phenomena contributing to acquired degenerative changes of the lumbosacral intervertebral segments as detailed in this discussion highlight the extraordinary problems that are associated with degenerative disease in this region of the spine. Further clinicoradiologic research in this area will progressively determine the clinical applications and clinical efficacy of the various traditional and newer methods of therapy in patients presenting with symptomatic acquired collapse of the intervertebral disks at and suprajacent to the lumbosacral junction and the interrelated degenerative alterations of the nondiskal structures of the spine.


The inner reality of the black man and his criminal responsibility.
Psychiatrists and psychologists are often requested by the legal fraternity to report on the mental state of Black people accused of an alleged crime. The question raised in this paper is whether personnel trained in the Western tradition, applying Western categories of mental states, are able to overcome their ethnocentricity. When the interviewer and the person interviewed are from widely different cultural groups, the former should make every effort to enter the inner world of the latter.


Use of leukocyte-depleted platelets and cytomegalovirus-seronegative red blood cells for prevention of primary cytomegalovirus infection after marrow transplant.
Seventy-seven cytomegalovirus (CMV)-seronegative marrow transplant patients were randomized in a prospective controlled trial comparing the use of leukocyte-depleted platelets plus CMV-seronegative red blood cells with standard unscreened blood products for the prevention of primary CMV infection during the first 100 days after transplant. Eligible patients included CMV-seronegative patients undergoing autologous transplant or seronegative patients undergoing allogeneic transplant for aplastic anemia or non-hematologic malignancy who had seronegative marrow donors. Patients and marrow donors were serologically screened for CMV and randomized before conditioning for transplant and followed for CMV infection with weekly cultures of throat, urine, and blood and with weekly CMV serologies until day 100 after transplant. Leukocyte-depleted platelets were prepared by centrifugation, a procedure that removed greater than 99% of leukocytes. There were no CMV infections observed in 35 evaluable treatment patients compared with seven infections in 30 evaluable control patients (P = .0013). There was no statistically significant difference in the mean number of platelet concentrates in the treatment patients (164 concentrates) compared with the control patients (126 concentrates). Leukocyte-depleted platelets plus CMV-seronegative red blood cells are highly effective in preventing primary CMV infection after marrow transplant.


Emotional aspects of anorexia nervosa: results of prospective naturalistic cognitive behavioral group therapy.
Anorexic girls have difficulties in handling their emotions. We examined emotional problems of adolescent girls with anorexia nervosa (AN) during the course of cognitive behavioral group therapy (G-CBT). Overall, 29 girls with AN (age 13-17 years) participated in four groups of manual based G-CBT. We assessed the body mass index (BMI), eating behavior psychopathology, emotions, depression, hedonistic activities, self-care and-efficacy, social phobia, sense of coherence (SOC), and alexithymia before, during and up to 1 year after therapy. Out of 29, 16 (55 %, intent to treat, or 76 %, per protocol) girls were successfully treated, 5 (17 or 24 %) had a "poor outcome", and 8 (28 %) dropped out. BMI, eating behavior, mood, social anxiety, self-care, and self-efficacy persistently improved. Anorexic girls had multiple emotional deficits, low self-confidence, and exaggerated needs of control and of being accepted. Emotional deficits were resistant to change. Hedonistic activities, social skills, and recovery from depression were positive, comorbid disorders and parental psychopathology negative prognostic factors.


Effects of fluvoxamine on nerve growth factor-induced neurite outgrowth inhibition by dexamethasone in PC12 cells.
In the present study, we examined the effects of fluvoxamine on nerve growth factor (NGF)-induced neurite outgrowth inhibition by dexamethasone (DEX) in PC12 cells. Fluvoxamine increased NGF-induced neurite outgrowth. Compared with co-treatment with NGF and fluvoxamine, p-Akt levels were higher than the values without fluvoxamine. The phosphorylated extracellular regulated kinase 1/2 levels were slightly increased by co-treatment with NGF and fluvoxamine. Fluvoxamine concentration-dependently improved NGF-induced neurite outgrowth inhibition by DEX. Fluvoxamine also improved the decrease in the NGF-induced p-Akt level caused by DEX. Interestingly, the sigma-1 receptor antagonist NE-100 blocked the improvement effects of fluvoxamine on NGF-induced neurite outgrowth inhibition by DEX. The selective sigma-1 receptor agonist PRE-084 also improved NGF-induced neurite outgrowth inhibition by DEX, which is blocked by NE-100. These results indicate that the improvement effects of fluvoxamine on NGF-induced neurite outgrowth inhibition by DEX may be attributable to the phosphorylation of Akt and the sigma-1 receptor.


Adverse pregnancy outcomes in rural Maharashtra, India (2008-09): a retrospective cohort study.
The study was carried out to record adverse pregnancy outcomes and to obtain information about sex ratio at birth in rural especially tribal areas in the State of Maharashtra, India. Although the tribal population is considered vulnerable to innumerable adversities, regretfully information about pregnancy wastage among them is not available. About 10% population of the state is tribal. The study of sex ratio at birth was planned as the overall sex ratio and child sex ratio had declined in the state. The cohort of antenatal cases registered in rural areas of Maharashtra in the calendar year 2008 was followed up to study the pregnancy outcomes. A retrospective study was carried out from October 2009 to August 2010. The outcomes of all the registered antenatal cases were recorded by the Auxiliary Nurse Midwives. The summary sheets were obtained by Block Medical Officers. The data was entered at the block level by trained data entry operators in specially designed web-based software. Adverse pregnancy outcome was categorized in two groups abortions and stillbirths. About 1.1 million registered pregnancies were followed up. In the state 5.34% registered pregnancies ended in abortions. In tribal PHCs the relative risk of spontaneous abortion and induced abortion was 0.91 and 0.38 respectively. It was also revealed that about 1.55% pregnancies culminated in stillbirth. The relative risk of stillbirths in tribal PHCs was 1.33. The sex ratio at birth in the state was 850. The ratio was 883 in the tribal PHCs. Correlation was observed between sex ratio at birth and induced abortion rate. The study indicates that women from tribal PHCs are exposed to higher risk of adverse pregnancy outcome in the form of stillbirths. In non-tribal areas high induced abortion rate and poor sex ratio at birth is observed. These two indicators are correlated. The correlation may be explained by the unscrupulous practice of sex selective abortion.


A biocultural approach to breastfeeding interactions in Central Africa.
Anthropologists have long recognized that breastfeeding involves much more than feeding; it entails intimate social interactions between infants or children and their mothers. However, breastfeeding has predominantly been studied with respect to structural features (frequency, timing) as well as nutritional and health aspects of infant feeding. Thus, in this study we complement previous anthropological studies by examining social interactions that occur during breastfeeding among the Aka and Bofi foragers and Ngandu and Bofi farmers at various ages (three to four months, nine to ten months, toddlers). Further, we use an integrated biocultural perspective to explore how patterns of breastfeeding and social interactions can be shaped by economic constraints, cultural values, and children's development. Overall, our findings illustrate how biological and cultural factors interact and provide useful explanations of variations in breastfeeding structure and social interactions more so than either perspective alone.


Biological activity of Ganoderma lucidum basidiocarps cultivated on alternative and commercial substrate.
Ganoderma lucidum (W. Curt.:Fr.) P. Karst. has been used for several thousand years in traditional medicine of the Far East for the treatment of a various diseases including: cancer, immunological disorders, hepatitis, arthritis, nephritis, bronchitis, asthma etc. Ganoderma species are natural sources of various antimicrobial, antioxidant and antitumor active compounds which can be alternative to commercial antibiotics, antimycotics, antioxidants and cytostatics. As the amount of wild Ganoderma lucidum basidiocarps is not sufficient, the aim of this study was to compare the bioactivity of basidiaocarps obtained on alternative substrate (wheat straw) with commercially cultivated ones. Antimicrobial potential of the tested Ganoderma lucidum extracts was studied by disc-diffusion and microdilution method. Cytotoxic effect of tested extracts on two cancer cell lines was determined by microculture tetrazolium test. DPPH scavenging ability, total phenols and flavonoids content were measured in order to determine the antioxidative potential of Ganoderma lucidum extracts. Ganoderma lucidum BEOFB 434 extract was the most effective antibacterial agent, while commercial strain was the weakest. DPPH· scavenging activity of extracts of basidiocarps from alternative substrate was also significantly higher than that of commercially obtained basidiocarps. The extracts of Ganoderma lucidum BEOFB 431 exhibited the strongest cytotoxic activity significantly higher than those in commercial strain. The study showed that fruiting bodies produced on one of the most accessible and cheapest crop residue, wheat straw, are better antimicrobial, antioxidant and cytotoxic agents than those obtained on conventional substrate, oak sawdust.


Investigating the relationship between prenatal growth and postnatal outcomes: a systematic review of the literature.
Theories regarding the relationship between pre- and postnatal growth and programming of health have been based on characteristics at birth, with little or no reference to the patterns of growth occurring in utero. Review of the literature to identify studies using ultrasonographically obtained fetal dimensions to track prenatal growth and relate these patterns of growth to postnatal anthropometry and cardiovascular and metabolic risk factors. Review of Medline, Scopus and Proquest for studies reporting on ultrasonographically derived estimates of fetal growth and their association with postnatal anthropometry, body composition or cardiovascular and metabolic risk factors. Quality of papers were assessed using the method developed by Downs and Black. Twenty-nine studies met the inclusion criteria, with a mean score of high quality. Twenty of the studies had follow-up in infancy, five in childhood, three in adolescence and one in adulthood. The associations observed suggest that centile tracking may occur early in pregnancy though whether this is as early as the first trimester is uncertain. The second trimester may be a critical period for the programming of blood pressure and abdominal circumference may be the most sensitive fetal dimension to indicate any programming.


Physical mapping of the srl recA region of Escherichia coli: analysis of Tn10 generated insertions and deletions.
A restriction endonuclease map for the enzymes EcoRI, BamHI, SalI, and PstI covering 23.5 kilobase pairs (kb) of the srl recA region of Escherichia coli was constructed. An insertion of the transposon Tn10 in the negative regulatory gene srlR was shown to be located 5.8 kb away from the promoter proximal end of the recA gene. The extent of several Tn10 generated deletions, originating from the srlR301::Tn10 insertion, were analyzed by physical mapping. Three mutations that had removed the Tn10 encoded tetracycline resistance gene, del(srl-recA)302, del(srl-recA)304, and del(srl-recA)303, were found to be deleted for 40%, 45%, and 50% of the recA structural gene, respectively. A deletion, del(srl-recA)306, that had not affected the structure of the Tn10 in srlR301 was shown to have removed the entire recA structural gene.


Trueness verification of actual creatinine assays in the European market demonstrates a disappointing variability that needs substantial improvement. An international study in the framework of the EC4 creatinine standardization working group.
The European In Vitro Diagnostics (IVD) directive requires traceability to reference methods and materials of analytes. It is a task of the profession to verify the trueness of results and IVD compatibility. The results of a trueness verification study by the European Communities Confederation of Clinical Chemistry (EC4) working group on creatinine standardization are described, in which 189 European laboratories analyzed serum creatinine in a commutable serum-based material, using analytical systems from seven companies. Values were targeted using isotope dilution gas chromatography/mass spectrometry. Results were tested on their compliance to a set of three criteria: trueness, i.e., no significant bias relative to the target value, between-laboratory variation and within-laboratory variation relative to the maximum allowable error. For the lower and intermediate level, values differed significantly from the target value in the Jaffe and the dry chemistry methods. At the high level, dry chemistry yielded higher results. Between-laboratory coefficients of variation ranged from 4.37% to 8.74%. Total error budget was mainly consumed by the bias. Non-compensated Jaffe methods largely exceeded the total error budget. Best results were obtained for the enzymatic method. The dry chemistry method consumed a large part of its error budget due to calibration bias. Despite the European IVD directive and the growing needs for creatinine standardization, an unacceptable inter-laboratory variation was observed, which was mainly due to calibration differences. The calibration variation has major clinical consequences, in particular in pediatrics, where reference ranges for serum and plasma creatinine are low, and in the estimation of glomerular filtration rate.


Study on Temper Embrittlement and Hydrogen Embrittlement of a Hydrogenation Reactor by Small Punch Test.
The study on temper embrittlement and hydrogen embrittlement of a test block from a 3Cr1Mo1/4V hydrogenation reactor after ten years of service was carried out by small punch test (SPT) at different temperatures. The SPT fracture energy Esp (derived from integrating the load-displacement curve) divided by the maximum load (Fm) of SPT was used to fit the Esp/Fm versus-temperature curve to determine the energy transition temperature (Tsp) which corresponded to the ductile-brittle transition temperature of the Charpy impact test. The results indicated that the ratio of Esp/Fm could better represent the energy of transition in SPT compared with Esp. The ductile-to-brittle transition temperature of the four different types of materials was measured using the hydrogen charging test by SPT. These four types of materials included the base metal and the weld metal in the as-received state, and the base metal and the weld metal in the de-embrittled state. The results showed that there was a degree of temper embrittlement in the base metal and the weld metal after ten years of service at 390 °C. The specimens became slightly more brittle but this was not obvious after hydrogen charging. Because the toughness of the material of the hydrogenation reactor was very good, the flat samples of SPT could not characterize the energy transition temperature within the liquid nitrogen temperature. Additionally, there was no synergetic effect of temper embrittlement and hydrogen embrittlement found in 3Cr1Mo1/4V steel.


A pre-post retrospective study of patients with cystic fibrosis and gastrostomy tubes.
The aim of the study was to assess the efficacy of gastrostomy tube (GT) placement on improving nutritional status and pulmonary function in patients with cystic fibrosis (CF). Data were collected from the Minnesota Cystic Fibrosis Database. Subjects with at least 5 percent-predicted forced expiratory volume in 1 second (ppFEV1) and 1 BMI percentile (pBMI) measurements before and after GT placement were included. Median pBMI values were compared 2 years before and 1, 2, and 4 years after GT placement using a signed rank test. Longitudinal mixed model analysis was used to assess the effect of GT placement on ppFEV1. To assess the effect of ppFEV1 at GT placement on efficacy, the estimated ppFEV1 change was regressed against the ppFEV1 level at placement. Forty-six subjects with CF who met entry criteria were identified. Mean estimated step changes in ppFEV1 at placement for men, women, boys, and girls were 2.16% (P = 0.52), 0.43% (P = 0.92), 0.99% (P = 0.65), and -0.91% (P = 0.74), respectively. Mean estimated slope changes of ppFEV1 after GT placement were 5.01% (P = 0.02), 4.48% (P = 0.07), 1.49% (P = 0.23), and 4.02% (P = 0.01) per year for men, women, boys, and girls, respectively. Median change in pBMI in the second year after GT placement was 13.3% (P ≤ 0.0001). Estimated coefficients for the effect of ppFEV1 level at placement on the ppFEV1 step and slope change were -0.041 (P = 0.28) and -0.005 (P = 0.84), respectively. GT placement in patients with CF results in significant improvement in both pBMI and ppFEV1, except in women. The change in lung function after GT placement is not dependent on the level of lung function at placement.


Vitamin C for preventing and treating the common cold.
The role of vitamin C (ascorbic acid) in the prevention and treatment of the common cold has been a subject of controversy for 60 years, but is widely sold and used as both a preventive and therapeutic agent. To discover whether oral doses of 0.2 g or more daily of vitamin C reduces the incidence, duration or severity of the common cold when used either as continuous prophylaxis or after the onset of symptoms. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2006); MEDLINE (1966 to December 2006); and EMBASE (1990 to December 2006). Papers were excluded if a dose less than 0.2 g per day of vitamin C was used, or if there was no placebo comparison. Two review authors independently extracted data and assessed trial quality. 'Incidence' of colds during prophylaxis was assessed as the proportion of participants experiencing one or more colds during the study period. 'Duration' was the mean days of illness of cold episodes. Thirty trial comparisons involving 11,350 study participants contributed to the meta-analysis on the relative risk (RR) of developing a cold whilst taking prophylactic vitamin C. The pooled RR was 0.96 (95% confidence intervals (CI) 0.92 to 1.00). A subgroup of six trials involving a total of 642 marathon runners, skiers, and soldiers on sub-arctic exercises reported a pooled RR of 0.50 (95% CI 0.38 to 0.66). Thirty comparisons involving 9676 respiratory episodes contributed to a meta-analysis on common cold duration during prophylaxis. A consistent benefit was observed, representing a reduction in cold duration of 8% (95% CI 3% to 13%) for adults and 13.6% (95% CI 5% to 22%) for children. Seven trial comparisons involving 3294 respiratory episodes contributed to the meta-analysis of cold duration during therapy with vitamin C initiated after the onset of symptoms. No significant differences from placebo were seen. Four trial comparisons involving 2753 respiratory episodes contributed to the meta-analysis of cold severity during therapy and no significant differences from placebo were seen. The failure of vitamin C supplementation to reduce the incidence of colds in the normal population indicates that routine mega-dose prophylaxis is not rationally justified for community use. But evidence suggests that it could be justified in people exposed to brief periods of severe physical exercise or cold environments.


Accurate and rapid detection of soil and fertilizer properties based on visible/near-infrared spectroscopy.
Accurate information of soil macronutrient contents and fertilizer macronutrient contents is the precondition of precision fertilization; however, how to detect soil and fertilizer information rapidly, reliably, and inexpensively remains a great challenge. Visible and near-infrared (VIS/NIR) diffuse reflectance spectroscopy proves to be an effective tool for extensive investigation of soil and fertilizer properties. This study first collected many soil and chemical fertilizer samples and performed both spectral scanning and chemical analysis. During the correlation between the collected VIS/NIR spectra and the measured data, different spectral pretreatment, sample selection, and wavelength optimization methods were applied for improving the accuracy and robustness of the prediction models. After appropriate spectral processing and selection of representative samples, both principal component regression and genetic algorithm (GA) can adequately reduce the number of variables and pick out the characteristic variables, which not only enhanced prediction speed but also greatly improved prediction accuracy. In particular, using GA-based models, organic matter content (OMC), total N and pH value in soil and N, P, and K contents in fertilizer can all be accurately predicted.


Post-licensure surveillance of trivalent live attenuated influenza vaccine in adults, United States, Vaccine Adverse Event Reporting System (VAERS), July 2005-June 2013.
Trivalent live attenuated influenza vaccine (LAIV3) was licensed and recommended for use in 2003 in children and adults 2-49 years of age. Post-licensure safety data have been limited, particularly in adults. We searched Vaccine Adverse Event Reporting System (VAERS) for US reports after LAIV3 from July 1, 2005-June 30, 2013 (eight influenza seasons) in adults aged ≥ 18 years old. We conducted descriptive analyses and clinically reviewed serious reports (i.e., death, life-threatening illness, hospitalization, prolonged hospitalization, or permanent disability) and reports of selected conditions of interest. We used empirical Bayesian data mining to identify adverse events (AEs) that were reported more frequently than expected. We calculated crude AE reporting rates to VAERS by influenza season. During the study period, VAERS received 1207 LAIV3 reports in adults aged 18-49 years old; 107 (8.9%) were serious, including four death reports. The most commonly reported events were expired drug administered (n=207, 17%), headache (n=192, 16%), and fever (n=133, 11%). The most common diagnostic categories for non-fatal serious reports were neurological (n=40, 39%), cardiovascular (n=14, 14%), and other non-infectious conditions (n=20, 19%). We noted a higher proportion of Guillain-Barré syndrome (GBS) and cardiovascular reports in the Department of Defense (DoD) population compared to the civilian population. Data mining detected disproportional reporting of ataxia (n=15); clinical review revealed that ataxia was a component of diverse clinical entities including GBS. Review of VAERS reports are reassuring, the only unexpected safety concern for LAIV3 identified was a higher than expected number of GBS reports in the DoD population, which is being investigated. Reports of administration of expired LAIV3 represent administration errors and indicate the need for education, training and screening regarding the approved indications.


Food Consumption Data as a Tool to Estimate Exposure to Mycoestrogens.
Zearalenone and alternariol are mycotoxins produced by Fusarium and Alternaria species, respectively, that present estrogenic activity and consequently are classified as endocrine disruptors. To estimate the exposure of the Portuguese population to these two mycotoxins at a national level, a modelling approach, based on data from 94 Portuguese volunteers, was developed considering as inputs: i) the food consumption data generated within the National Food and Physical Activity Survey; and ii) the human biomonitoring data used to assess the exposure to the referred mycotoxins. Six models of association between mycoestrogens urinary levels (zearalenone, total zearalenone and alternariol) and food items (meat, cheese, and fresh-cheese, breakfast cereals, sweets) were established. Applying the obtained models to the consumption data (n = 5811) of the general population, the median estimates of the probable daily intake revealed that a fraction of the Portuguese population might exceed the tolerable daily intake defined for zearalenone. A reference intake value for alternariol is still lacking, thus the characterization of risk due to the exposure to this mycotoxin was not possible to perform. Although the unavoidable uncertainties, these results are important contributions to understand the exposure to endocrine disruptors in Portugal and the potential Public Health consequences.


Is adrenalectomy necessary during unilateral nephrectomy for Wilms Tumor? A report from the Children's Oncology Group.
To determine whether performing adrenalectomy at the time of nephrectomy for unilateral Wilms tumor impacts clinical outcome. We reviewed information on all patients enrolled on National Wilms Tumor Study-4 and -5. Data were abstracted on patient demographics, tumor characteristics, surgical and pathologic status of the adrenal gland, and patient outcomes. The primary endpoints were intraoperative spill and five-year event-free survival (EFS) in patients who did or did not undergo adrenalectomy. Of 3825 patients with complete evaluable data, the adrenal was left in situ in 2264 (57.9%) patients, and was removed completely in 1367 patients (36.7%) or partially in 194 patients (5.2%). Of the adrenal glands removed, 68 (4.4%) contained tumor. Adrenal involvement was more common in patients with stage 3 (9.8%) than stage 2 disease (1.9%; p < 0.0001). After controlling for stage and histopathology, five-year EFS was similar whether or not the adrenal gland was removed (p = 0.48), or involved with tumor (p = 0.81); however, intraoperative spill rates were higher in patients undergoing adrenalectomy (26.1% vs 15.5%, p < 0.0001), likely due to larger tumor size or technical factors. No patient had clinical evidence of adrenal insufficiency or tumor recurrence in the adrenal gland during follow-up (median 9.9 years). Sparing the adrenal gland during nephrectomy for unilateral Wilms tumor was not associated with a higher incidence of intraoperative spill and was associated with a similar oncologic outcome, on a per-stage basis, with cases where the adrenal was removed. Thus, adrenalectomy should not be considered mandatory during radical nephrectomy for Wilms tumor.


A phase Ib/II and pharmacokinetic study of EP0057 (formerly CRLX101) in combination with weekly paclitaxel in patients with recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer.
EP0057 (formerly CRLX101) is an investigational nanoparticle-drug conjugate (NDC) of a cyclodextrin-based polymer backbone plus camptothecin, a topoisomerase-1 inhibitor. Prior studies showed efficacy in recurrent or persistent, epithelial ovarian, fallopian tube or primary peritoneal cancer (EOC). This phase Ib/2 trial assessed safety and efficacy of EP0057 Q2W plus weekly paclitaxel in patients with EOC. The recommended phase 2 dose (RP2D) was identified using a 3+3 design. The single-arm phase 2 assessed overall response (ORR) per RECIST 1.1 in patients previously treated with bevacizumab. Secondary objectives included progression free survival (PFS) and duration of response. The RP2D was established as 15 mg/m2 EP0057 Q2W plus 80 mg/m2 paclitaxel administered 3 weeks on/1 week off. Nine patients enrolled on phase 1b, with no DLTs; 21 additional patients enrolled on phase 2. All completed >1 cycle. Median age was 62 (44-76) years, 57% ≥3 prior therapies. For the primary analysis, 6/19 patients with prior bevacizumab had confirmed responses (ORR=31.6% (95% CI: 15.4% to 54.0%)) including one complete response (CR). Median PFS was 5.4 months. Most common grade 3/4 adverse events attributed to treatment were decreased neutrophil count (13, 43%) and anemia (3, 10%). Although the observed ORR was not statistically better than the historical control rate, EP0057 remains an interesting option for treatment of recurrent EOC. EP0057 exhibits high plasma drug retention, slow clearance, and controlled slow release of CPT from the polymer when administered alone and with paclitaxel. (NCT02389985) 242 words.


Use of residence time moments in compartmental analysis.
Residence time moments, particularly mean residence times, can be very useful in the modeling and kinetic analysis of physiological systems. They are defined and illustrated, and their practical utility is then explored by comparing the model formulation based on these moments with three alternative formulations: component half-lives, compartmental model rate coefficients, and multiexponential model coefficients and exponents. The residence time moment formulation is shown to have several advantages: a smaller number of parameters are usually needed to describe a biological system; they have a clear physical interpretation; their statistical "power" to detect certain treatment differences is greater; and they are computationally simpler in many situations.


[Patient care in an out-of-hours care practice - a descriptive study of the CONTENT project].
Little published research is available about the content of out of hours care (OOHC) in Germany. CONTENT is a project of the University Hospital Heidelberg to build up a morbidity registry for ambulatory health care. One of the participating practices of the network is a rural OOHC centre. The study reports exemplarily on the work of this practice. The design of the study is cross-sectional. One of the 2 available CONTENT practice-softwares was used for data retrieval. The softwares allow for classifying reasons for encounter (RFE), health problems (diagnoses) and processes of care with the International Classification of Primary Care (ICPC-2). Furthermore the softwares allow for pseudonymised data export. A 3-year period with 15 886 patient contacts of 9 542 patients (65.9% female) is described. Close to 8% of the population in the catchment area visited the practice at least once in a year. Medium age of the patients was 42 years (range 0-104). The groups of the 25-44-year-old and the 45-64-year-old patients formed together 43% of all contacts. The most frequent RFE were: fever (5.8%), sore throat (4.8%), cough (4.8%), earache (3.9%) and insect bites (3.6%). Frequencies of these RFEs differed considerably between the age groups. With the help of the data, resulting diagnoses and care processes can be described in detail. This study describes, for the first time in Germany, the work of an OOHC practice. Data capture to accomplish this was feasible within existing practice software and without much extra work. If more OOHC practices would participate in the CONTENT project a more representative picture of OOHC in Germany could be established.


Advances in the Production and Application of Induced Pluripotent Stem Cells.
Embryonic stem cells are pluripotent, meaning they have the capacity to selfrenew and to differentiate into cells of the 3 germ layers. In 2006, Takahashi et al. reprogrammed somatic cells into stem cells using exogenetic gene expression. These new cells became known as induced pluripotent stem cells (iPSCs). Research continues to develop new tools and techniques in order to reprogram cells with higher output and quality, so that iPSCs can be used in modeling of human disorders, drug discovery and of course, regenerative medicine. After a brief overview of the basic characteristics of iPSCs, this article will cover the production and processing techniques of these cells, with a focus on new innovations, as well as their different uses and potential role in future research. Progress over the last few years regarding the efficient and safe ways to produce iPSCs has been tremendous. These cells might open doors regarding the future of precision medicine practices and research.


Review on vocational predictors: a systematic review of predictors of vocational outcomes among individuals with schizophrenia: an update since 1998.
Predictors of employment outcomes of individuals with schizophrenia have continued to be studied over the past decade with implications for the development of vocational interventions to help the mentally ill get and keep jobs. A total of 62 relevant studies since 1998 were systematically reviewed by means of meta-analysis and frequency counts. Frequency count allowed all 62 studies to be included, whereas the meta-analysis excluded studies with inadequate information but made it possible to estimate the magnitude of effects. Both methods resulted in similar findings. In contrast to an earlier review, cognitive functioning received overwhelming support as a significant predictor. Other significant predictors included education, negative symptoms, social support and skills, age, work history (previous history of successful employment), and rehabilitation service to restore community functioning and well-being by occupational therapists, psychiatrists, psychologists, social workers and other mental health professionals. Positive symptoms, substance abuse, gender and hospitalization history were found to be non-significant predictors. The frequency count did not support marital status as a significant predictor but the meta-analysis did. This review highlights increasing sophistication in understanding the links between individual characteristics and functional impairments. It also suggests that more research is needed into other potentially important predictors that may be changeable and relate to recovery. These include attitudes and beliefs about disability payments and psychological processes such as self-stigmatization, negative beliefs, and social skills deficits for which intervention may be possible.


Three-Decade Evaluation of Cerebrospinal Fluid Pressure in Open-Angle Glaucoma at a Tertiary Care Center.
Elevated intraocular pressure (IOP) is the most prevalent risk factor for primary open-angle glaucoma. However, IOP alone does not fully describe a mechanical basis for disease in patients with normal tension glaucoma or primary open-angle glaucoma. The translaminar pressure difference (TLPD) theory proposes that the pressure gradient generated by the difference of IOP and cerebrospinal fluid pressure (CSFp) acting at the level of the optic nerve can lead to cupping and glaucoma when IOP is higher than normal and/or CSFp is lower than normal. The study results to date have generally supported the TLPD theory; however, varying methods, populations, and sample sizes make it difficult to compare results. To further assess whether there is an association between low CSFp and open-angle glaucoma, 30 years of clinical data that assess 96,543 lumbar punctures were analyzed. Patients with open-angle glaucoma showed a significantly lower CSFp than randomly selected normal control patients (9.9 ± 3 mm·Hg (n = 86) versus 12.1 ± 3.6 mm·Hg (n = 114), p < 0.001) following adjustment for age and sex. This retrospective study provides strong evidence for an association between open-angle glaucoma and low CSFp.


Clinical Features Of Acute Febrile Thrombocytopaenia Among Patients Attending Primary Care Clinics.
Identifying clinical features that differentiate acute febrile thrombocytopaenia from acute febrile illness without thrombocytopaenia can help primary care physician to decide whether to order a full blood count (FBC). This is important because thrombocytopaenia in viral fever may signify more serious underlying aetiology like dengue infection. The aim of this study was to compare the clinical features of acute febrile patients with thrombocytopaenia and acute febrile patients without thrombocytopaenia. This was a clinic-based cross-sectional study from May to November 2003. Consecutive patients presenting with undifferentiated fever of less than two weeks were selected from the Primary Care Centre of Hospital Universiti Kebangsaan Malaysia and Batu 9 Cheras Health Clinic. Clinical features of these patients were recorded and FBC examination was done for all patients. Thrombocytopaenia was defined as platelet count <150X10(9)/L. The odds ratio of thrombocytopaenia for each presenting symptoms was calculated. Seventy-three patients participated in this study. Among them, 45.2% had thrombocytopaenia. Myalgia and headache were common among all patients. However, nausea and vomiting occurred significantly more often among patients with thrombocytopaenia than in patients with normal platelet count (OR 2.2, 95% CI 1.1-4.5). Acute non-specific febrile patients presenting with symptoms of nausea and vomiting may have higher risk of thrombocytopaenia and should be seriously considered for FBC. viral infection, dengue, clinical features, thrombocytopaenia.


Acetabular morphology in bladder exstrophy complex.
Little information is available concerning the acetabular morphology in adults with a history of bladder exstrophy. We documented the pelvic anatomy in adult patients with bladder exstrophy who never had prior surgery. We retrospectively reviewed 31 patients (62 hips) seen from 1976 to 2003 for urologic problems related to bladder exstrophy without adjunctive pelvic osteotomy. There were 18 males and 13 females with an average age of 30 years at last followup. Radiographs at final followup were analyzed for lateral center-edge angle, acetabular index, head extrusion, hip center of rotation, acetabular version, retroversion index, sacral width, and interteardrop distance. Most hips (60 hips) had no arthritis. The average lateral center-edge angle, ace-tabular index, and head extrusion index were 32 degrees, 5.7 degrees, and 0.266%, respectively. Fifty-eight percent of hips had a retroverted acetabulum and 42% were neutral or anteverted. The interteardrop distance averaged 154 mm. Most patients will not have early arthritis develop, and the majority of patients (58%) have retroverted orientation of the acetabulum.


A new magnetic state selection method in high-performance optically detected compact cesium beam clocks.
We perform a new scheme of magnetic state selection in optically detected compact cesium beam clocks. Unlike the conventional method, we select atoms in the ground state |F = 4, mF ≠ -4⟩ by pointing the atomic collimator to the convex pole of the magnet realizing the two-wire magnetic field and detect atoms in |F = 3⟩ after interacting with the microwave field using a distributed feedback laser. The fluorescence background is greatly reduced as the inherent residual atoms |F = 4, mF = -4⟩ are avoided in this reversed scheme. The velocity distribution is narrowed, and the most probable velocity is decreased, since atomic trajectories are close to the weak-field region. We also investigate the relationship between the position of the atomic collimator and the distributions of the atomic beam, which is consistent with the Monte Carlo-based simulation model. By applying the reversed scheme and setting the deviated position of the collimator to 1.3 mm, the signal contrast is improved from 0.7 to 3, and the short-term frequency stability reaches 3.0 × 10-12 τ-1/2, nearly three times better than that of the high-performance version of Microsemi 5071A.


Flexibility of individual multitasking strategies in task-switching with preview: are preferences for serial versus overlapping task processing dependent on between-task conflict?
The prevalence and the efficiency of serial and parallel processing under multiple task demands are highly debated. In the present study, we investigated whether individual preferences for serial or overlapping (parallel) processing represent a permanent predisposition or depend on the risk of crosstalk between tasks. Two groups (n = 91) of participants were tested. One group performed a classical task switching paradigm, enforcing a strict serial processing of tasks. The second group of participants performed the same tasks in a task-switching-with-preview paradigm, recently introduced by Reissland and Manzey (2016), which in principle allows for overlapping processing of both tasks in order to compensate for switch costs. In one condition, the tasks included univalent task stimuli, whereas in the other bivalent stimuli were used, increasing risk of crosstalk and task confusion in case of overlapping processing. The general distinction of voluntarily occurring preferences for serial or overlapping processing when performing task switching with preview could be confirmed. Tracking possible processing mode adjustments between low- and high-crosstalk conditions showed that individuals identified as serial processors in the low-crosstalk condition persisted in their processing mode. In contrast, overlapping processors split up in a majority adjusting to a serial processing mode and a minority persisting in overlapping processing, when working with bivalent stimuli. Thus, the voluntarily occurring preferences for serial or overlapping processing seem to depend at least partially on the risk of crosstalk between tasks. Strikingly, in both crosstalk conditions the individual performance efficiency was the higher, the more they processed in parallel.


Effects of 1-year anti-TNF-α therapies on bone mineral density and bone biomarkers in rheumatoid arthritis and ankylosing spondylitis.
Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have been associated with generalized and localized bone loss. We conducted a comprehensive study using imaging (dual-energy X-ray absorptiometry, DXA) and laboratory biomarkers in order to determine bone health and to study the effects of anti-tumor necrosis factor (TNF) biologics in RA and AS. Thirty-six RA and 17 AS patients undergoing 1-year etanercept (ETN) or certolizumab-pegol (CZP) therapy were studied. Bone density was assessed by DXA at baseline and after 12 months. Serum C-reactive protein (CRP), calcium, phosphate, parathyroid hormone (PTH), vitamin D3, osteocalcin, procollagen type I N-propeptide (P1NP), C-terminal telopeptide (βCTX), osteoprotegerin, sclerostin (SOST), Dickkopf-1 (DKK-1), soluble receptor activator nuclear kappa B ligand (sRANKL), and cathepsin K (cathK) levels were determined at baseline and after 6 and 12 months. TNF-α inhibition was clinically effective. Anti-TNF-α halted further bone loss over 1 year. In general, anti-TNF therapy significantly increased P1NP, SOST levels, and the P1NP/βCTX ratios, while decreased DKK-1 and CathK production at different time points in most patient subsets. In the full cohort and in RA, baseline and/or 12-month bone mineral density (BMD) at multiple sites exerted inverse relationships with CRP and βCTX, and positive correlation with SOST. In AS, L2-4 BMD after 1-year biologic therapy inversely correlated with baseline βCTX, while femoral neck BMD rather showed inverse correlations with CRP. Anti-TNF therapy slowed down generalized bone loss, in association with clinical improvements, in both diseases. TNF blockade may enhance bone formation and suppress joint destruction. Anti-TNF therapy may act inversely on DKK-1 and SOST. Independent predictors of BMD were SOST and βCTX in RA, whilst CRP in AS.Key Points• One-year anti-TNF therapy halted generalized bone loss in association with clinical improvement in arthritides.• Anti-TNF therapy may inversely act on DKK-1 and SOST.• Independent predictors of BMD were SOST and βCTX in RA, while CRP in AS.


CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs.
The proper function of immune surveillance requires well-coordinated mechanisms in order to guide the patrolling immune cells through peripheral tissues and into secondary lymphoid organs. Analyzing gene-targeted mice, we identified the chemokine receptor CCR7 as an important organizer of the primary immune response. CCR7-deficient mice show severely delayed kinetics regarding the antibody response and lack contact sensitivity and delayed type hypersensitivity reactions. Due to the impaired migration of lymphocytes, these animals reveal profound morphological alterations in all secondary lymphoid organs. Upon activation, mature skin dendritic cells fail to migrate into the draining lymph nodes. Thus, in order to bring together lymphocytes and dendritic cells to form the characteristic microarchitecture of secondary lymphoid organs, CCR7 is required to rapidly initiate an adoptive immune response.


Transgenic Expression of Human Thrombomodulin Inhibits HMGB1-Induced Porcine Aortic Endothelial Cell Activation.
Transgenic expression of human thrombomodulin (hTBM), which has the potential to solve the problem of coagulation dysregulation in pig-to-primate xenotransplantation, may have additional benefits by neutralizing the proinflammatory cytokine high-mobility group box 1 (HMGB1). The aim of this study was to investigate HMGB1-mediated effects on porcine aortic endothelial cells (PAEC) from wild-type (WT) and hTBM transgenic pigs. Porcine aortic endothelial cells were treated with HMGB1, human (h)TNFα or lipopolysaccharide (LPS). Procoagulant and proinflammatory responses were assessed by measuring expression of cell surface markers (adhesion molecules, fibrinogen-like protein 2, plasminogen activator inhibitor (PAI)-1), secretion of porcine cytokines and chemokines (HMGB1, TNFα, IL-8, monocyte chemotactic protein-1), and formation of PAI-1/tissue plasminogen activator complexes. Thrombin-mediated degradation of HMGB1 in the presence of PAEC was examined by Western blot and functional assay. High-mobility group box 1 potently activated WT PAEC, increasing the expression of E-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, fibrinogen-like protein 2, and PAI-1, the secretion of TNFα, IL-8, and monocyte chemotactic protein-1 and the formation of PAI-1/tissue plasminogen activator complexes. Human TNFα- or LPS-induced activation of WT PAEC was inhibited by treatment with rabbit anti-HMGB1 antibody. Transgenic expression of hTBM significantly reduced the activation of PAEC by HMGB1 or hTNFα, and significantly enhanced thrombin-induced HMGB1 cleavage. Chemically induced shedding of the lectin-like domain of TBM resulted in significantly increased HMGB1-induced PAEC activation. High-mobility group box 1 exerts powerful proinflammatory and procoagulant effects on WT PAEC, and appears to be an important downstream mediator for the actions of hTNFα and LPS. Human thrombomodulin transgenic PAECs are less sensitive to activation by either HMGB1 or hTNFα, an effect that appears to be dependent on the lectin-like domain of TBM.


Risk Assessment Using Risk Scores in Patients with Acute Coronary Syndrome.
Risk scores are widely used in patients with acute coronary syndrome (ACS) prior to treatment decision-making at different points in time. At initial hospital presentation, risk scores are used to assess the risk for developing major adverse cardiac events (MACE) and can guide clinicians in either discharging the patients at low risk or swiftly admitting and treating the patients at high risk for MACE. During hospital admission, risk assessment is performed to estimate mortality, residual ischemic and bleeding risk to guide further in-hospital management (e.g., timing of coronary angiography) and post-discharge management (e.g., duration of dual antiplatelet therapy). In the months and years following ACS, long term risk can also be assessed to evaluate current treatment strategies (e.g., intensify or reduce pharmaceutical treatment options). As multiple risk scores have been developed over the last decades, this review summarizes the most relevant risk scores used in ACS patients.


Complex optical constants on a subwavelength scale.
Optical phase contrast has for the first time been observed on a nanometer scale, with a near-field microscope of scattering type that maps the complete optical field of amplitude and phase. Backed by quasielectrostatic theory, we demonstrate the significance and experimental accessibility of even complex optical constants on a subwavelength scale. Further, our method can separate the near-field response from background artifacts and thus is expected to enable nanoscale optical mapping of even topography-rich objects such as resonant clusters and macromolecules.


Use of physician-recommended non-pharmacological strategies for hypertension control among hypertensive patients.
This study aims to evaluate the 4 non-pharmacological strategies adopted by patients for hypertension control and patient characteristics that affect the choice of strategies. Four thousand hypertensive patients aged ≥18 years were selected from the National Health and Nutrition Examination Survey. Odds ratios of the choice of strategies were analyzed using weighted logistic models. Clinical recommendations of non-pharmacological strategies for hypertension control were relatively low. More exercise was the least frequent strategy used for hypertension control. More patients reported using ≥3 strategies than using ≤2 strategies (79.1% vs 20.9%, P < .0001). Non-Hispanic blacks were more likely to use each individual strategy and to use ≥3 strategies simultaneously. Patients with obesity and diabetes were less likely to attempt weight control or more exercise, but more likely to use ≥3 strategies than peers. Educational programs should be developed to enhance physician's advice for lifestyle modifications and to increase patient's acceptance of physical activity.


Bovine intestinal cellular responses following primary and challenge infections with Calicophoron microbothrium metacercariae.
This study was carried out to establish whether cattle can develop resistance to re-infection by Calicophoron microbothrium by assessing the response of intestinal mucosal globule leukocytes, eosinophils, mast cells and basophils, and the establishment of the parasite in the host. A total of 24 1-year-old Tuli steers were randomly divided into four groups of six animals each and infected with C. microbothrium metacercariae. On the first day of the study, animals in Groups I and II were immunized with 5000 metacercariae and then challenged with 15,000 metacercariae on Day 150 post-immunization. Animals in Group III were immunized with 15,000 metacercariae at the same time that Groups I and II animals were challenged to act as a positive control group. Animals in Group IV were left uninfected and acted as a negative control group. Three animals from each group were slaughtered on Day 28 post-challenge and the remainder were slaughtered on Day 42 post-challenge. The established amphistomes were recovered and histopathological and cytological examinations were done on the jejunum, duodenum, abomasum and the rumen. The establishment rates of the challenge infection in the immunized and challenged groups were lower and ranged from 0 to 0.2% as compared to 6% from naive animals infected as positive controls. Animals immunized and then challenged with C. microbothrium had significantly higher eosinophil, mast cell and globule leukocytes counts in the intestinal mucosa (P < 0.05) as compared to those of the control group. The study indicates that cattle can develop resistance to C. microbothrium re-infection and that eosinophils and mast cells may be important cells in the rejection of the parasite.


Structural insights into central hypertension regulation by human aminopeptidase A.
Hypertension is regulated through both the central and systemic renin-angiotensin systems. In the central renin-angiotensin system, zinc-dependent aminopeptidase A (APA) up-regulates blood pressure by specifically cleaving the N-terminal aspartate, but not the adjacent arginine, from angiotensin II, a process facilitated by calcium. Here, we determined the crystal structures of human APA and its complexes with different ligands and identified a calcium-binding site in the S1 pocket of APA. Without calcium, the S1 pocket can bind both acidic and basic residues through formation of salt bridges with the charged side chains. In the presence of calcium, the binding of acidic residues is enhanced as they ligate the cation, whereas the binding of basic residues is no longer favorable due to charge repulsion. Of the peptidomimetic inhibitors of APA, amastatin has higher potency than bestatin by fitting better in the S1 pocket and interacting additionally with the S3' subsite. These results explain the calcium-modulated substrate specificity of APA in central hypertension regulation and can guide the design and development of brain-targeting antihypertensive APA inhibitors.


The tourniquet in total knee arthroplasty. A prospective, randomised study.
We assessed the influence of the use of a tourniquet in total knee arthroplasty in a prospective, randomised study. After satisfying exclusion criteria, we divided 77 patients into two groups, one to undergo surgery with a tourniquet and one without. Both groups were well matched. The mean change in knee flexion in the group that had surgery without a tourniquet was significantly better at one week (p = 0.03) than in the other group, but movement was similar at six weeks and at four months. There was no significant difference in the surgical time, postoperative pain, need for analgesia, the volume collected in the drains, postoperative swelling, and the incidence of wound complications or of deep-venous thrombosis. We conclude that the use of a tourniquet is safe and that current practice can be continued.


A phase I clinical and pharmacokinetic trial of hepsulfam.
Hepsulfam (1,7-heptanediol-bis-sulfamate) is one of a series of bis-sulfamate acid esters that was synthesized in an attempt to improve the antitumor efficacy of busulfan. Hepsulfam has shown broad antineoplastic activity in preclinical studies. This Phase I trial evaluated hepsulfam given as a single i.v. dose every 21-35 days. Twenty-nine patients with refractory solid tumors participated in this study. Twenty-six of these patients had had either prior chemotherapy or radiation therapy. Fifty-two courses of treatment were given at doses ranging from 30 to 360 mg/m2/day. The dose limiting toxicity was prolonged thrombocytopenia and granulocytopenia. This toxicity was cumulative with Grade 3 or 4 thrombocytopenia occurring in 3 of 15, 4 of 9, and 2 of 2 patients in the first, second, and third courses of greater than or equal to 210 mg/m2, respectively. This toxicity was noted in patients with less than or equal to 1 prior chemotherapeutic regimen, as well as in patients with greater than 1 prior chemotherapeutic regimens. Nonhematological toxicities included Grade 1 or 2 nausea and vomiting and fatigue. There was no evidence of pulmonary toxicity. Plasma levels of hepsulfam were quantified by gas chromatography in 12 patients. The plasma and blood half-lives were 15.9 +/- 4.6 and 90 +/- 13 h, respectively. No objective tumor responses were seen. We conclude that the maximally tolerated dose when hepsulfam is given as a single dose every 35 days is 210 mg/m2, but that there is significant risk of cumulative hematological toxicity at this level.


Early Targeting of L-Selectin on Leukocytes Promotes Recovery after Spinal Cord Injury, Implicating Novel Mechanisms of Pathogenesis.
L-selectin, a lectin-like receptor on all leukocyte classes, functions in adhesive and signaling roles in the recruitment of myeloid cells from the blood to sites of inflammation. Here, we consider L-selectin as a determinant of neurological recovery in a murine model of spinal cord injury (SCI). Spinal cord-injured, L-selectin knock-out (KO) mice (male) showed improved long-term recovery with greater white matter sparing relative to wild-type (WT) mice and reduced oxidative stress in the injured cord at 72 h post-SCI. There was a partial and transient reduction in accumulation of neutrophils in the injured spinal cords of KOs at 24 h post-injury. To complement these findings with KO mice, we sought a pharmacologic means for lowering L-selectin levels. We found that diclofenac, a nonsteroidal anti-inflammatory drug (NSAID), induced the shedding of L-selectin from the cell surface of myeloid subsets, specifically neutrophils and non-classical monocytes, in the blood and the injured spinal cord. Diclofenac administration to injured WT mice enhanced neurological recovery to a level comparable to that of KOs but did not improve recovery in KOs. While diclofenac treatment had no effect on myeloid cell accumulation, there was a reduction in oxidative stress at 72 h post-SCI. These findings implicate L-selectin in secondary pathogenesis beyond a role in leukocyte recruitment and raise the possibility of repurposing diclofenac for the treatment of SCI.


NK1 receptor expression in the interstitial cells of Cajal and neurons and tachykinins distribution in rat ileum during development.
The origin and function of the interstitial cells of Cajal (ICCs) that are located at the level of the deep muscular plexus (DMP) have not been completely identified. It has been recently reported that these cells express neurokinin-1 (NK1) receptors to which substance P (SP) shows the highest affinity. Studies during pre- and postnatal life have demonstrated that ICCs are identifiable in the rat ileum soon after birth and already show adult features at 7 days of postnatal life. Several neurotransmitters have been identified at the DMP which appear at specific times during development. We have studied the expression of NK1 receptors by ICCs and enteric neurons and the timing of the appearance of SP in the DMP, myenteric plexus (MP) and submucous plexus (SMP) of rat ileum during development. Rats, aged from 18 days of fetal life to adulthood, were used. NK1 receptors and SP were identified by using NK1 polyclonal antibodies and tachykinin (SP/TK) polyclonal antibodies, respectively. NK1-immunoreactivity (IR) was detected in the ICCs immediately after birth and reached maximal intensity at 7 days. From birth, SP/TK-IR fibers originated from short excitatory neurons at the MP and reached the DMP at 1 week of postnatal life. NK1- and SP/TK-IR appeared in the MP neurons in the fetus and in the SMP neurons at weaning. The present study demonstrates that by the first days of postnatal life, the NK1-IR might be used as a marker of the ICCs at the DMP and suggests that these cells may participate in the actions exerted by tachykinins on muscle cells.


Brain spectrin(240/235) and brain spectrin(240/235E): differential expression during mouse brain development.
Mouse brain contains at least 2 distinct spectrin subtypes: brain spectrin(240/235) and brain spectrin(240/235E) (Riederer et al., 1986). In this study, we demonstrate that these subtypes are differentially expressed during mouse brain development. Brain spectrin(240/235) can be detected in fetal tissue and increases 2-fold during brain development. This subtype is enriched in the cortical cytoplasm of germinative neural cells and is also found in fibers resembling axons as early as fetal life. Brain spectrin(240/235E), which is specifically detected with antibodies to red blood cell spectrin, is below the limits of detection in fetal and neonatal brain but rapidly increases in concentration during the second postnatal week. Brain spectrin(240/235E) is confined to the cell body and dendrites of differentiating neurons and to glial cells but is not expressed in mitotic cells. This subtype is most prominent in granule cells of the cerebellum and dentate gyrus in the hippocampus.


[Familial combined hyperlipidemia].
Familial combined hyperlipidemia is a common inherited disorder characterized by a hepatic overproduction of apo B particles and an elevated risk for the development of atherosclerosis. LDL particles are smaller and denser and are more prone to oxidation. The exact pathogenesis of familial combined hyperlipidemia is unclear at present. Treatment should aim to reduce the synthesis of atherogenic lipoproteins and to increase the clearance of triglyceride-rich lipoproteins.


Tumor-derived autophagosome vaccine: mechanism of cross-presentation and therapeutic efficacy.
We previously reported that autophagy in tumor cells plays a critical role in cross-presentation of tumor antigens and that autophagosomes are efficient antigen carriers for cross-priming of tumor-reactive CD8(+) T cells. Here, we sought to characterize further the autophagosome-enriched vaccine named DRibble (DRiPs-containing blebs), which is derived from tumor cells after inhibition of protein degradation, and to provide insights into the mechanisms responsible for their efficacy as a novel cancer immunotherapy. DRibbles were characterized by Western blot and light or transmission electron microscopy. The efficiency of cross-presentation mediated by DRibbles was first compared with that of whole-tumor cells and pure proteins. The mechanisms of antigen cross-presentation by DRibbles were analyzed, and the antitumor efficacy of the DRibble vaccine was tested in 3LL Lewis lung tumors and B16F10 melanoma. The DRibbles sequester both long-lived and short-lived proteins, including defective ribosomal products (DRiP), and damage-associated molecular pattern molecules exemplified by HSP90, HSP94, calreticulin, and HMGB1. DRibbles express ligands for CLEC9A, a newly described C-type lectin receptor expressed by a subset of conventional and plasmacytoid dendritic cells (DC), and cross-presentation was partially CLEC9A dependent. Furthermore, this autophagy-assisted antigen cross-presentation pathway involved both caveolae- and clathrin-mediated endocytosis and endoplasmic reticulum-associated degradation machinery. It depends on proteasome and TAP1, but not lysosome functions of antigen-presenting cells. Importantly, DCs loaded with autophagosome-enriched DRibbles can eradicate 3LL Lewis lung tumors and significantly delay the growth of B16F10 melanoma. These data documented the unique characteristics and potent antitumor efficacy of the autophagosome-based DRibble vaccine. The efficacy of DRibble cancer vaccine will be further tested in clinical trials.


Virion incorporation of integrin α4β7 facilitates HIV-1 infection and intestinal homing.
The intestinal mucosa is a key anatomical site for HIV-1 replication and CD4+ T cell depletion. Accordingly, in vivo treatment with an antibody to the gut-homing integrin α4β7 was shown to reduce viral transmission, delay disease progression, and induce persistent virus control in macaques challenged with simian immunodeficiency virus (SIV). We show that integrin α4β7 is efficiently incorporated into the envelope of HIV-1 virions. Incorporated α4β7 is functionally active as it binds mucosal addressin cell adhesion molecule-1 (MAdCAM-1), promoting HIV-1 capture by and infection of MAdCAM-expressing cells, which in turn mediate trans-infection of bystander cells. Functional α4β7 is present in circulating virions from HIV-infected patients and SIV-infected macaques, with peak levels during the early stages of infection. In vivo homing experiments documented selective and specific uptake of α4β7+ HIV-1 virions by high endothelial venules in the intestinal mucosa. These results extend the paradigm of tissue homing to a retrovirus and are relevant for the pathogenesis, treatment, and prevention of HIV-1 infection.


Performing (heterosexual) femininity: female agency and role in sexual life and contraceptive use - a qualitative study in Australia.
Women's liberation and the sexual revolution have changed the social landscape for heterosexual women in the West over the past 50 years, but exploration of women's lived experiences of contraceptive use in the context of their sexual lives is comparatively recent. We conducted 94 in-depth open-ended interviews with women of reproductive age (16-49 years) living in New South Wales, Australia. Interviews were audio-recorded, transcribed verbatim and analysed using an inductive thematic approach. Four major themes are explored here: (1) what women do and do not do: unspoken gendered assumptions; (2) focus on partner's pleasure; (3) juggling responsibilities: sex as a chore; and (4) women's sexual motivations. Findings suggest sexual double standards and gender expectations continue to pervade women's sexual and contraceptive practices. We found that women performed their femininity by focusing on enabling their male partner's pleasure, while simultaneously ignoring their own sexual desires, wishes or interests. Accompanying new-found freedoms are new-found responsibilities, as women now add managing modern contraceptives and a good sex life to their list of tasks alongside paid employment, domestic labour and childrearing. Our research findings suggest that women may derive different pleasures from sex, including what we term 'connection pleasure'.


Unusual steroid specificity of the cell surface progesterone receptor on human sperm.
The steroid specificity of the cell surface progesterone receptor in human sperm was examined with the use of progesterone, testosterone, and androstane analogues. Many compounds were shown to be more effective than progesterone at increasing intracellular free calcium concentration, e.g., 2 alpha-methyl-17beta-methoxy-5 alpha-androstan-3-one. Several testosterone analogues were demonstrated to be antagonists of progesterone, e.g., 9(11)-dehydro-2 alpha,17alpha-dimethyltestosterone. The synthetic potent progestigens, norethynodrel, cyproterone acetate, norethindrone, and megestrol acetate, were found to be only weak stimulators of the sperm cell surface receptor. Furthermore, these compounds were shown to antagonize the effect of progesterone to elevate intracellular free calcium concentration in sperm. It is known that progesterone and some of its analogues bind to the intracellular progesterone nuclear receptor via the alpha-face of the steroid molecule. In stark contrast, it was concluded from the analysis of the steroid analogues examined on human sperm in this study that intimate contact exists between the effective progesterone analogues and the sperm cell surface progesterone receptor across the beta-face of the steroid C/D-ring "upper" edge (C11, C12, and C17). Positioning of the C21 methyl group is also critical for efficacy, and recognition of the steroid A-ring seems not to be involved.


US of the snapping iliopsoas tendon.
To determine the value of ultrasound (US) in the diagnosis of snapping iliopsoas tendon. In three patients, dynamic US of the hip was performed as the flexed, abducted, and externally rotated hip was extended. The contralateral hip was also evaluated. Hip arthrography was performed in all three patients, magnetic resonance imaging in two, and iliopsoas bursography in two, which was successful in only one case. One patient underwent surgical release of the iliopsoas tendon. At US, an abnormal jerk of the iliopsoas tendon during hip motion was correlated with the painful audible snap. The motion of the contralateral iliopsoas tendon was smooth. No intraarticular abnormality was found in two patients, and an associated labral tear was suspected at arthrography in the third patient. The patient who underwent surgical release of the iliopsoas tendon had great improvement. US is a useful dynamic noninvasive technique for the diagnosis of snapping iliopsoas tendon.


High Adherence to Iron/Folic Acid Supplementation during Pregnancy Time among Antenatal and Postnatal Care Attendant Mothers in Governmental Health Centers in Akaki Kality Sub City, Addis Ababa, Ethiopia: Hierarchical Negative Binomial Poisson Regression.
Iron deficiency during pregnancy is a risk factor for anemia, preterm delivery, and low birth weight. Iron/Folic Acid supplementation with optimal adherence can effectively prevent anemia in pregnancy. However, studies that address this area of adherence are very limited. Therefore, the current study was conducted to assess the adherence and to identify factors associated with a number of Iron/Folic Acid uptake during pregnancy time among mothers attending antenatal and postnatal care follow up in Akaki kality sub city. Institutional based cross-sectional study was conducted on a sample of 557 pregnant women attending antenatal and postnatal care service. Systematic random sampling was used to select study subjects. The mothers were interviewed and the collected data was cleaned and entered into Epi Info 3.5.1 and analyzed by R version 3.2.0. Hierarchical Negative Binomial Poisson Regression Model was fitted to identify the factors associated with a number of Iron/Folic Acid uptake. Adjusted Incidence rate ratio (IRR) with 95% confidence interval (CI) was computed to assess the strength and significance of the association. More than 90% of the mothers were supplemented with at least one Iron/Folic Acid supplement from pill per week during their pregnancy time. Sixty percent of the mothers adhered (took four or more tablets per week) (95%CI, 56%-64.1%). Higher IRR of Iron/Folic Acid supplementation was observed among women: who received health education; which were privately employed; who achieved secondary education; and who believed that Iron/Folic Acid supplements increase blood, whereas mothers who reported a side effect, who were from families with relatively better monthly income, and who took the supplement when sick were more likely to adhere. Adherence to Iron/Folic Acid supplement during their pregnancy time among mothers attending antenatal and postnatal care was found to be high. Activities that would address the above mentioned factors were highly recommended to ensure the sustainability of mothers' adherence to the supplement.


[Vacuum-assisted closure therapy for the treatment of acute postoperative osteomyelitis].
Vacuum-assisted closure is used frequently for the treatment of posttraumatic osteomyelitis of the extremities. After debridement and repeated VAC dressing changes, the wounds are closed by secondary suture, split-thickness skin grafts or local flaps. However, no objective parameters describe the time point for secondary wound closure. Our thesis was that negative microbiological results from bone specimens can indicate the time for secondary wound closure. Moreover, treatment course and clinical outcome after 3.4 years should be compared to those of other surgical approaches for acute postoperative osteomyelitis from the literature. 43 patients with acute postoperative osteomyelitis of the extremities and the pelvis were treated by serial bone and soft tissue debridements and VAC therapy and analysed prospectively. Debridements were repeated until the wounds were macroscopically free from signs of infection (good granulation/no necrosis). During each revision a bone specimen was taken for microbiological analysis. Number of revisions, bacterial cultures, type of wound closure and recurrence of infection after 3 years and 5 months on average after the last surgery was analysed. 9.8 debridements on average were performed until eradication of infection and secondary wound closure. Despite the absence of macroscopic infection, bacteria were still found in bone samples from 15 of 43 patients. Three biopsies were free of bacteria for the first time right before wound closure, 25 samples had become negative during the treatment. Six recurrences (19.3 %) were noted after 3.4 years on average. Four patients from the group of negative bone biopsies (19 %) and two patients from the group of persisting bacteria before secondary closure (20 %) had a recurrence of infection. In about one third of the bone biopsies bacteria persisted. This bacterial load had no correlation to wound healing and rate of recurrence after over 3 years. In conclusion, microbiological bone samples are not suitable as an indicator for the time point of secondary wound closure. Compared to other treatment options in acute postoperative osteomyelitis from the literature (especially implantation of local antibiotics), no advantage of vacuum-assisted closure could be shown concerning number of debridements and rate of recurrences.


Laryngeal tube as airway rescue device from prehospital tracheostomy: a case report.
Airway management is a priority for the critically ill patient. The insertion of a cuffed tracheal tube is the best practice to obtain an airway control; however, it is associated with many practical problems in prehospital trauma care. When this common procedure is not available, it can be substituted by an extraglottic airway. We report the case of a 54-year-old victim of a multi-vehicle collision brought to the Emergency Department of a Level One Trauma Center by Emergency Medical Service. Initial evaluation revealed a Glasgow Coma Scale score of 8 and a fixed and midriatic right pupil, suggesting a severe head injury. The patient did not show any predictable sign of difficult intubation. After oxygen administration and cervical spine immobilization a rapid sequence induction was carried out and intubation failed after three attempts. Then a laryngeal tube (LT) was successfully placed and connected with a transport ventilator. The transfer to the hospital took 20 minutes with SpO(2) level of 99% and end tidal carbon dioxide not above 42 mmHg. The patient was properly ventilated by the LT during the computed tomography scan investigations. Due to the impossibility of endotracheal intubation the patient underwent surgical tracheostomy as suggested by the ear nose throat surgeon consultant. This case suggests that LT could be an important alternative device for airway management in trauma patients after a failed tracheal intubation. LT is a precious tool to achieve good ventilation and oxygenation from the field to the operatory theatre.


Impact of tumour characteristics and cancer treatment on cerebrovascular mortality after glioma diagnosis: Evidence from a population-based cancer registry.
We aimed to examine brain tumour grade, a marker of biological aggressiveness, tumour size and cancer treatment are associated with cerebrovascular mortality among patients with malignant glioma, the most common and aggressive type of brain tumour. We conducted a retrospective, observational cohort study using the US National Cancer Institute's state and regional population-based cancer registries. We identified adult patients with glioma in 2000 to 2018 (N=72,916). The primary outcome was death from cerebrovascular disease. Cox regression modelling was used to estimate the associations with cerebrovascular mortality of tumour grade, tumour size and treatment (surgery, radiotherapy, chemotherapy), calculating hazard ratios (HR) adjusted for these factors as well as for age, sex, race, marital status and calendar year. Higher grade (Grade IV vs Grade II: HR=2.47, 95% CI=1.69-3.61, p<0.001) and larger brain tumours (size 3 to <6 cm: HR=1.40, 95% CI=1.03 -1.89, p<0.05; size ≥ 6 cm: HR=1.47, 95% CI=1.02-2.13, p<0.05 compared to size < 3cm) were associated with increased cerebrovascular mortality. Cancer treatment was associated with decreased risk (surgery: HR= 0.60, p<0.001; chemotherapy: HR=0.42, p<0.001; radiation: HR= 0.69, p<0.05). However, among patents surviving five years or more from cancer diagnosis radiotherapy was associated with higher risk of cerebrovascular mortality (HR 2.73, 95% CI 1.49-4.99, p<0.01). More aggressive tumour characteristics are associated with increased cerebrovascular mortality. Radiotherapy increased risk of cerebrovascular mortality five-year after cancer diagnosis. Further research is needed to better understand the long-term cardiovascular consequences of radiation therapy, and whether the consequent risk can be mitigated.